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BioAssay: AID 624119

qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): CYP 2D6

The covalent attachment of a phosphopantetheinyl (4'-PP) arm to a variety of synthases and other proteins is a key posttranslational protein modification. The 4'-PP is installed on the proteins post-translationally from coenzyme A (CoA) on a conserved serine residue by action of phosphopantetheinyl transferase (PPTase) enzymes. Phosphopantetheinylation is essential for synthase activity, and more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 624119
Data Source: NCGC (PPTA910)
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2012-05-01
Hold-until Date: 2013-04-30
Modify Date: 2013-04-30

Data Table ( Complete ):           View All Data
Tested Compound:
Related Experiments
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AIDNameTypeComment
1819Probe Development Summary of Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase)Summarydepositor-specified cross reference: Summary AID
1490qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase)Confirmatorysame project related to Summary assay
2701Confirmation qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase)Confirmatorysame project related to Summary assay
2707Gel-Based Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase)Confirmatorysame project related to Summary assay
493214Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Dry Powder FollowupConfirmatorysame project related to Summary assay
540350qHTS Assay for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization FollowupConfirmatorysame project related to Summary assay
540352qHTS for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization Followup in B. Subtilis 168Confirmatorysame project related to Summary assay
540353qHTS for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization Followup in B. Subtilis HM489Confirmatorysame project related to Summary assay
540355Gel-Based Assay for Inhibitos of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Chemistry Optimization FollowupConfirmatorysame project related to Summary assay
602360qHTS Assay for Inhibitors of Bacillus subtilis AcpS phosphopantetheinyl transferase (PPTase): SARConfirmatorysame project related to Summary assay
602362qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Gel Based AssayConfirmatorysame project related to Summary assay
602366qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR in B subtilis HM489Confirmatorysame project related to Summary assay
602370qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR Round 2Confirmatorysame project related to Summary assay
602371qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR in B subtilis 168Confirmatorysame project related to Summary assay
602373qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Hepg2 AssayConfirmatorysame project related to Summary assay
602391qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): SAR in hGST A1-1Confirmatorysame project related to Summary assay
602392qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Label Free Assay for SAROthersame project related to Summary assay
602479qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Mouse Liver Microsome Stability (Half Time)Othersame project related to Summary assay
602480qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Aqueous Solubility in PBSOthersame project related to Summary assay
624112qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Aqueous Solubility in PBSOthersame project related to Summary assay
624113qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): Mouse Plasma StabilityOthersame project related to Summary assay
624118qHTS Assay for Inhibitors of Bacillus subtilis Sfp phosphopantetheinyl transferase (PPTase): CYP 3A4Othersame project related to Summary assay
Description:
The covalent attachment of a phosphopantetheinyl (4'-PP) arm to a variety of synthases and other proteins is a key posttranslational protein modification. The 4'-PP is installed on the proteins post-translationally from coenzyme A (CoA) on a conserved serine residue by action of phosphopantetheinyl transferase (PPTase) enzymes. Phosphopantetheinylation is essential for synthase activity, and removal of the PPTase gene precludes natural product synthesis in microorganisms, or in the case of fatty acid biosynthesis, renders the organism unviable. PPTase enzymes belong to a distinct structural superfamily. Within bacteria, these enzymes are grouped into two classes based upon primary structure, the AcpS-Type and Sfp-Type PPTases.

Sfp-type PPTases, corresponding to an activator of surfactin production in Bacillus subtilis, are responsible for modifying type I polyketide and nonribosomal peptide synthases of prokaryotes. Sfp-type PPTases are responsible for the activation of a variety of pathogen-associated virulence factors. Among these compounds are toxins such as mycolactone from Mycobacterium ulcerans, siderophores such as vibriobactin from Vibrio cholerae or mycobactin from Mycobacterium tuberculosis, as well as the mycolic acids which form the waxy cell wall of Mycobacteria. The biosyntheses of these natural products are considered attractive targets for drug design.

After a large qHTS and several follow-up assays, a small molecule was identified and this in vitro ADME assay serves to better characterize its properties. This profiling assay looks at the compounds susceptibility to be metabolized by Cytochrome 2D6, an important drug metabolizing enzyme.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]

MLPCN Grant: MH083226
Assay Submitter (PI): Michale Burkart, University of California, San Diego
Protocol
This assay was carried out by a contracted research organization.
Comment
Compounds are "inactive" if percent inhibition at 3 uM compound concentration is <= 30%; compounds are "inconclusive" if > 30% or < 50% inhibition; compounds are "active" if >= 50%. It is desirable for compounds to be inactive as this indicates that compounds are not metabolized by CYP 2D6.
Activity score is percent inhibition.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1CYP 2D6 % Inhibition at 3 uM Float%
2Compound QCString
Additional Information
Grant Number: MH083226

Data Table (Concise)
Data Table ( Complete ):     View All Data
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